scholarly journals PIK3CA Mutations Are Not Correlated With Worse Disease-Free Survival in Early-Stage Cervical Cancer Treated With Surgery and Could be a Target for Overcoming Resistance to Chemoradiotherapy in Locally Advanced Cervical Cancer

Author(s):  
Z.A. Oaks ◽  
K. Tucker ◽  
B. Beaty ◽  
V. Bae-Jump ◽  
A.A. Weiner
2013 ◽  
Vol 23 (5) ◽  
pp. 877-883 ◽  
Author(s):  
Philippe Tummers ◽  
Amin Makar ◽  
Katrien Vandecasteele ◽  
Gert De Meerleer ◽  
Hannelore Denys ◽  
...  

IntroductionSince the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervical cancer (LACC) have improved but are still disappointing. Therefore, the idea of surgery after chemoradiation in case of LACC or bulky disease was adopted. One of the concerns regarding surgery following chemoradiotherapy is surgery-related morbidity.AimThe objectives of this study were to investigate the feasibility of surgery after advanced radiotherapy techniques such as intensity-modulated arc therapy (IMAT) and to describe the morbidity.MethodsThis was a prospective study of primary inoperable LACC patients primary treated with IMAT, in most cases combined with weekly cisplatin. Then the resectability was reevaluated. If resectable patients were treated with Wertheim type 2 surgery ± pelvic lymphadenectomy (on positron emission tomography–computed tomography indication). If tumor is not resectable, patients were treated with brachytherapy.ResultsSince 2006, 41 consecutive patients were included. After neoadjuvant IMAT, 34 were considered resectable and underwent surgery, whereas 7 proceeded with brachytherapy. The operative mortality rate was nil. There were no major perioperative complications. No ureter, bladder, or bowel injuries occurred. No postoperative urinary/digestive fistulae or stenoses were noted. Eleven patients had postoperatively urinary retention problems. At the time of discharge, 5 patients still needed self-catheterization. All problems resolved within 3 months. In 4 cases, we saw significant lymphoceles. In all patients intended to treat, overall survival and disease-free survival at 3 years were 63% and 74%. In the Wertheim group, overall survival and disease-free survival at 3 years were 81% and 91%.ConclusionsCompleting surgery after chemoradiation therapy (with IMAT) for LACC or bulky disease is feasible, and complication rates are comparable with those of primary surgery for cervical cancer.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15541-e15541
Author(s):  
George Au-Yeung ◽  
Linda R. Mileshkin ◽  
David Bernshaw ◽  
Srinivas Kondalsamy-Chennakesavan ◽  
Danny Rischin ◽  
...  

e15541 Background: Definitive treatment with concurrent cisplatin and radiation is the standard of care for locally advanced cervical cancer. The optimal management of patients with a contraindication to cisplatin has not been established. We conducted a retrospective audit of the impact of concurrent chemoradiation in a cohort of patients (pts) with locally advanced cervical cancer. Methods: All pts with locally advanced cervical cancer treated with definitive radiation were entered into a prospective database. Information regarding their demographics, stage, histology, recurrence and survival were recorded. Pharmacy records were reviewed to determine concurrent chemotherapy use. The primary endpoint was overall survival, and secondary endpoints were disease free survival and rates of primary, nodal or distant failure. Univariate and multivariate analyses were performed, incorporating known prognostic factors of age, FIGO stage, uterine body involvement, tumour volume on MRI and nodal involvement. Results: 442 pts were treated from Jan 1996 to Feb 2011. Median age was 59 (range 22-94); 89% had squamous histology and 64% node-negative disease. 269 pts received cisplatin, 59 received carboplatin because of a contraindication to cisplatin and 114 received no concurrent chemotherapy (most prior to 1999). Overall survival adjusted for other prognostic factors was significantly improved with use of concurrent cisplatin compared to radiation alone (HR 0.53, p=0.001), as was disease free survival and the rate of distant failure. Use of concurrent carboplatin was not associated with any significant benefit compared to radiation alone in terms of overall survival or disease free survival on univariate or multivariate analyses. Conclusions: The results of this audit are consistent with the known significant survival benefit with concurrent cisplatin chemoradiation. However, there did not appear to be any significant benefit associated with concurrent carboplatin although there are potential confounding factors in this small cohort. The available evidence in the literature favors the use of non-platinum chemotherapy rather than carboplatin in pts with contraindications to cisplatin.


Trials ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Jing Li ◽  
Hua Liu ◽  
Ya Li ◽  
Jian Li ◽  
Lifei Shen ◽  
...  

Abstract Background Currently, the standard treatment for locally advanced cervical cancer is concurrent chemoradiation (CCRT). The effect of neoadjuvant chemotherapy in advanced cervical cancer is controversial. Studies have shown that the addition of a weekly regimen of neoadjuvant chemotherapy (NACT) followed by CCRT may be superior to a thrice-weekly regimen of NACT and CCRT. Among patients who had not received prior cisplatin, a cisplatin and paclitaxel (TP) regimen resulted in longer overall survival than other regimens. This study aims to investigate the feasibility, safety, and efficacy of NACT with weekly TP followed by CCRT. Methods This is a prospective, randomized, open-labeled, multicentered phase III study. Based on a 65% of 2-year disease-free survival (DFS) rate in the CCRT group and 80% of that in NACT followed by CCRT group, and on prerequisite conditions including an 8% loss to follow-up, a two-sided 5% of type I error probability, and an 80% of power, a total of 300 cases were required for enrollment. Patients with IIB–IVA cervical cancer will be randomly allocated in a 1:1 ratio to one of two intervention arms. In the study arm, patients will receive dose-dense cisplatin (40 mg/m2) and paclitaxel (60 mg/m2) weekly for 4 cycles followed by CCRT (45 Gy in 5 weeks concurrent with cisplatin 40 mg/m2 weekly) plus image-guided adaptive brachytherapy (IGBRT). In the control arm, patients will undergo CCRT treatment. The primary endpoint of the study is 2-year disease-free survival (DFS); the secondary endpoints are 5-year overall survival (OS) and disease-free survival (DFS), the response rate 3 months after treatment completion, grade III/IV adverse effects, and quality of life, and potential biomarkers for predicting treatment response will also be studied. Discussion The data gathered from the study will be used to determine whether NACT with weekly TP followed by CCRT may become an optimized treatment for locally advanced cervical cancer. Trial registration Chinese Clinical Trial Registry ChiCTR1900025327. Registered on 24 August 2019. medresman.org.cn ChiCTR1900025326


2019 ◽  
Vol 29 (1) ◽  
pp. 42-47 ◽  
Author(s):  
Guler Yavas ◽  
Cagdas Yavas ◽  
Erdem Sen ◽  
Irem Oner ◽  
Cetin Celik ◽  
...  

IntroductionStandard treatment for locally advanced cervical cancer (LACC) includes concomitant chemoradiotherapy (CRT) that typically controls localized disease. However, most patients develop distant metastasis, ultimately leading to death.ObjectiveTo determine the role of adjuvant carboplatin and paclitaxel for clinical outcomes in patients with LACC.MethodsBetween 2010 and 2017, 109 patients with LACC were retrospectively evaluated. All patients received cisplatin (40 mg/m2) with concurrent external-beam radiotherapy (up to 50.4 Gy), followed by intra-cavitary brachytherapy. Forty-six of 109 patients received a median of six cycles (range 3–6 cycles) of adjuvant chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (CRT + chemotherapy group; area under the curve 5). The remaining 63 patients did not receive adjuvant chemotherapy (CRT group).ResultsDisease-free survival and overall survival after a median follow-up of 24.5 months (range 2.6–94.75 months) were 93.5% and 95.7% and 69.8% and 82.5 % for the CRT + chemotherapy and CRT groups, respectively (p = 0.001, p = 0.012, respectively). No acute grade 3/4 gastrointestinal or genitourinary toxicities were seen during CRT. During adjuvant chemotherapy, the most troublesome side effects were hematologic and neurologic toxicities; however, most were manageable. No chronic grade 3/4 genitourinary toxicities were seen.DiscussionAdjuvant chemotherapy in patients with LACC significantly improved both disease-free survival and overall survival without increasing unmanageable toxicity. Future larger prospective trials are warranted to verify these findings.


2020 ◽  
Vol 30 (12) ◽  
pp. 1855-1861 ◽  
Author(s):  
Simone Marnitz ◽  
Audrey Tieko Tsunoda ◽  
Peter Martus ◽  
Marcelo Vieira ◽  
Renato Jose Affonso Junior ◽  
...  

ObjectiveRevised staging of patients with locally advanced cervical cancer is based on clinical examination, imaging, and potential surgical findings. A known limitation of imaging techniques is an appreciable rate of understaging. In contrast, surgical staging may provide more accurate information on lymph node involvement. The aim of this prospective study was to evaluate the impact of pre-treatment surgical staging, including removal of bulky lymph nodes, on disease-free survival in patients with locally advanced cervical cancer.MethodsUterus-11 was a prospective international multicenter study including patients with locally advanced cervical cancer who were randomized 1:1 to surgical staging (experimental arm) or clinical staging (control arm) followed by primary platinum-based chemoradiation. Patients with histologically proven squamous cell carcinoma, adenocarcinoma, or adenosquamous cancer International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IIB–IVA underwent gynecologic examination and pre-treatment imaging including abdominal computed tomography (CT) and/or abdominal magnetic resonance imaging (MRI). Patients had chest imaging (any of the following: X-ray, CT, or PET-CT). The primary endpoint was disease-free survival and the secondary endpoint was overall survival. An ad hoc analysis was performed after trial completion for cancer-specific survival. Randomization was conducted from February 2009 to August 2013.ResultsA total of 255 patients (surgical arm, n=130; clinical arm, n=125) with locally advanced cervical cancer were randomized. Of these, 240 patients were eligible for analysis. The two groups were comparable with respect to patient characteristics. The surgical approach was transperitoneal laparoscopy in most patients (96.6%). Laparoscopic staging led to upstaging in 39 of 120 (33%) patients. After a median follow-up of 90 months (range 1–123) in both arms, there was no difference in disease-free survival between the groups (p=0.084). For patients with FIGO stage IIB, surgical staging is superior to clinical staging with respect to disease-free survival (HR 0.51, 95% CI 0.30 to 0.86, p=0.011). In the post-hoc analysis, surgical staging was associated with better cancer-specific survival (HR 0.61, 95% CI 0.40 to 0.93, p=0.020).ConclusionOur study did not show a difference in disease-free survival between surgical and clinical staging in patients with locally advanced cervical cancer. There was a significant benefit in disease-free survival for patients with FIGO stage IIB and, in a post-hoc analysis, a cancer-specific survival benefit in favor of laparoscopic staging. The high risk of distant metastases in both arms emphasizes the need for further evaluation.


2020 ◽  
Author(s):  
Amanda Veiga-Fernández ◽  
María López-Altuna ◽  
Ignacio Romero-Martínez ◽  
Elsa Mendizábal Vicente ◽  
Patricia Rincon Olbes ◽  
...  

2021 ◽  
pp. ijgc-2020-002086
Author(s):  
Juliana Rodriguez ◽  
Jose Alejandro Rauh-Hain ◽  
James Saenz ◽  
David Ortiz Isla ◽  
Gabriel Jaime Rendon Pereira ◽  
...  

IntroductionRecent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy.MethodsWe performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models.ResultsA total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8–201.2) in the laparoscopic group and 52.6 months (range, 0.4–166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09–2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05–4.37; P=0.03).ConclusionIn this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.


2019 ◽  
Vol 30 (2) ◽  
pp. 181-186 ◽  
Author(s):  
Benoit Bataille ◽  
Alexandre Escande ◽  
Florence Le Tinier ◽  
Audrey Parent ◽  
Emilie Bogart ◽  
...  

ObjectiveThe standard of care for early cervical cancer is radical hysterectomy; however, consideration of pre-operative brachytherapy has been explored. We report our experience using pre-operative brachytherapy plus Wertheim-type hysterectomy to treat early stage cervical cancer.MethodsThis single-center study evaluated consecutive patients with histologically proven node-negative early stage cervical cancer (International Federation of Gynecology and Obstetrics 2009 stage IB1–IIB) that was treated using pre-operative brachytherapy and hysterectomy. Pre-brachytherapy staging was performed using magnetic resonance imaging (MRI) and pelvic lymph node assessment was performed using lymphadenectomy. The tumor and cervical tissues were treated using brachytherapy (total dose 60 Gy) followed by Wertheim-type hysterectomy. The study included patients from January 2000 to December 2013.ResultsA total of 80 patients completed a median follow-up of 6.7 years (range 5.4–8.5). The surgical specimens revealed a pathological complete response for 61 patients (76%). Patients with incomplete responses generally had less than 1 cm residual tumor at the cervix, and only one patient had lymphovascular space involvement. The estimated 5-year rates were 88% for overall survival (95% CI 78% to 94%) and 82% for disease-free survival (95% CI 71% to 89%). Toxicities were generally mild-to-moderate, including 26 cases (33%) of grade 2 late toxicity and 10 cases (13%) of grade 3 late toxicity. Univariate analyses revealed that poor disease-free survival was associated with overweight status (≥25 kg/m2, HR 3.05, 95% CI 1.20 to 7.76, p=0.019) and MRI tumor size >3 cm (HR 3.05, 95% CI 1.23 to 7.51, p=0.016).ConclusionsPre-operative brachytherapy followed by Wertheim-type hysterectomy may be safe and effective for early stage cervical cancer, although poorer outcomes were associated with overweight status and MRI tumor size >3 cm.


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